Abstract：
:Glucose-stimulated insulin secretion from the islet beta-cell involves a sequence of metabolic events and an interplay between a wide range of signaling pathways leading to the generation of second messengers (e.g., cyclic nucleotides, adenine and guanine nucleotides, soluble lipid messengers) and mobilization of calcium ions. Consequent to the generation of necessary signals, the insulin-laden secretory granules are transported from distal sites to the plasma membrane for fusion and release of their cargo into the circulation. The secretory granule transport underlies precise changes in cytoskeletal architecture involving a well-coordinated cross-talk between various signaling proteins, including small molecular mass GTP-binding proteins (G proteins) and their respective effector proteins. The purpose of this article is to provide an overview of current understanding of the identity of small G proteins (e.g., Cdc42, Rac1, and ARF-6) and their corresponding regulatory factors (e.g., GDP/GTP-exchange factors, GDP-dissociation inhibitors) in the pancreatic beta-cell. Plausible mechanisms underlying regulation of these signaling proteins by insulin secretagogues are also discussed. In addition to their positive modulatory roles, certain small G proteins also contribute to the metabolic dysfunction and demise of the islet beta-cell seen in in vitro and in vivo models of impaired insulin secretion and diabetes. Emerging evidence also suggests significant insulin secretory abnormalities in small G protein knockout animals, further emphasizing vital roles for these proteins in normal health and function of the islet beta-cell. Potential significance of these experimental observations from multiple laboratories and possible avenues for future research in this area of islet research are highlighted.
journal_name
Endocr Revjournal_title
Endocrine reviewsauthors
Kowluru Adoi
10.1210/er.2009-0022subject
Has Abstractpub_date
2010-02-01 00:00:00pages
52-78issue
1eissn
0163-769Xissn
1945-7189pii
er.2009-0022journal_volume
31pub_type
杂志文章,评审abstract：:Recent identification of new selenocysteine-containing proteins has revealed relationships between the two trace elements selenium (Se) and iodine and the hormone network. Several selenoproteins participate in the protection of thyrocytes from damage by H(2)O(2) produced for thyroid hormone biosynthesis. Iodothyronine...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2001-0034
更新日期：2005-12-01 00:00:00
abstract：:Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antipro...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2011-1015
更新日期：2012-08-01 00:00:00
abstract：:Vitamin D deficiency is common in the elderly, especially in the housebound and in geriatric patients. The establishment of strict diagnostic criteria is hampered by differences in assay methods for 25-hydroxyvitamin D. The synthesis of vitamin D3 in the skin under influence of UV light decreases with aging due to ins...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/edrv.22.4.0437
更新日期：2001-08-01 00:00:00
abstract：:Loss of estrogens or androgens increases the rate of bone remodeling by removing restraining effects on osteoblastogenesis and osteoclastogenesis, and also causes a focal imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. Conversely, androge...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2003-0003
更新日期：2004-06-01 00:00:00
abstract：:Pregnancy dramatically affects the hypothalamic-pituitary-adrenal axis leading to increased circulating cortisol and ACTH levels during gestation, reaching values in the range seen in Cushing's syndrome (CS). The cause(s) of increased ACTH may include placental synthesis and release of biologically active CRH and ACTH...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2004-0025
更新日期：2005-10-01 00:00:00
abstract：:Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) belong to the steroid/thyroid hormone receptor superfamily. Cloning of their cDNAs demonstrated the existence of two distinct but related genes: COUP-TFI (EAR-3, NR2F1) and COUP-TFII (ARP-1, NR2F2). They are referred to as orphan receptors because li...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2010-0021
更新日期：2011-06-01 00:00:00
abstract：:Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected. However, about 50% of Eur...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2009-0011
更新日期：2009-06-01 00:00:00
abstract：:Osteoclasts and osteoblasts dictate skeletal mass, structure, and strength via their respective roles in resorbing and forming bone. Bone remodeling is a spatially coordinated lifelong process whereby old bone is removed by osteoclasts and replaced by bone-forming osteoblasts. The refilling of resorption cavities is i...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2007-0014
更新日期：2008-04-01 00:00:00
abstract：:Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2015-1104
更新日期：2016-10-01 00:00:00
abstract：:There is a large body of literature showing that prolactin (PRL) exerts growth-promoting activities in breast cancer, and possibly in prostate cancer and prostate hyperplasia. In addition, increasing evidence argues for the involvement of locally produced (autocrine) PRL, perhaps even more than pituitary-secreted (end...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2004-0016
更新日期：2005-05-01 00:00:00
abstract：:It is well known that GH is important in the regulation of longitudinal bone growth. Its role in the regulation of bone metabolism in man has not been understood until recently. Several in vivo and in vitro studies have demonstrated that GH is important in the regulation of both bone formation and bone resorption. In ...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/edrv.19.1.0324
更新日期：1998-02-01 00:00:00
abstract：OBJECTIVE:To summarize controlled trials examining the effect of calcium on bone density and fractures in postmenopausal women. DATA SOURCE:We searched MEDLINE and EMBASE up to 1998 and the Cochrane Controlled Register up to 2000, and we examined citations of relevant articles and proceedings of international meetings...
journal_title：Endocrine reviews
pub_type： 杂志文章,meta分析,评审
doi：10.1210/er.2001-7002
更新日期：2002-08-01 00:00:00
abstract：:Members of the TGF-beta superfamily, which includes TGF-betas, growth differentiation factors, bone morphogenetic proteins, activins, inhibins, and glial cell line-derived neurotrophic factor, are synthesized as prepropeptide precursors and then processed and secreted as homodimers or heterodimers. Most ligands of the...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2002-0003
更新日期：2002-12-01 00:00:00
abstract：:The major goal of this review is to summarize recent exciting findings that have been published within the past 10 years that, to our knowledge, have not been presented in detail in previous reviews and that may impact altered follicular development in polycystic ovarian syndrome (PCOS) and premature ovarian failure i...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2017-00164
更新日期：2018-02-01 00:00:00
abstract：:Insulin signaling plays a physiological role in traditional insulin target tissues controlling glucose homeostasis as well as in pancreatic β-cells and in the endothelium. Insulin signaling abnormalities may, therefore, be pathogenic for insulin resistance, impaired insulin secretion, endothelial dysfunction, and even...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2011-1042
更新日期：2012-08-01 00:00:00
abstract：:There has been an alarming increase in the prevalence of obesity in people with type 1 diabetes in recent years. Although obesity has long been recognized as a major risk factor for the development of type 2 diabetes and a catalyst for complications, much less is known about the role of obesity in the initiation and p...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2017-00191
更新日期：2018-10-01 00:00:00
abstract：:The etiology of the AITDs remains unclear but it is now generally believed that both genetic and environmental factors contribute to their development. Some recent findings have begun to directly and indirectly implicate the possibility of infectious agents in the pathogenesis of AITD, and these data serve as the basi...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/edrv-14-1-107
更新日期：1993-02-01 00:00:00
abstract：:In recent years, ovarian tissue cryopreservation has rapidly developed as a successful method for preserving the fertility of girls and young women with cancer or benign conditions requiring gonadotoxic therapy, and is now becoming widely recognized as an effective alternative to oocyte and embryo freezing when not fe...
journal_title：Endocrine reviews
pub_type： 杂志文章
doi：10.1210/endrev/bnaa020
更新日期：2020-12-01 00:00:00
abstract：:Substantial advances have been made recently in the pathobiology of pituitary tumors. Similar to many other endocrine tumors, over the last few years we have recognized the role of germline and somatic mutations in a number of syndromic or nonsyndromic conditions with pituitary tumor predisposition. These include the ...
journal_title：Endocrine reviews
pub_type： 杂志文章
doi：10.1210/endrev/bnaa006
更新日期：2020-12-01 00:00:00
abstract：:People with type 2 diabetes are disproportionately affected by cardiovascular disease (CVD), compared with those without diabetes. Traditional risk factors do not fully explain this excess risk, and other "nontraditional" risk factors may be important. This review will highlight the importance of nontraditional risk f...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2002-0034
更新日期：2004-02-01 00:00:00
abstract：:Investigations of biological programs that are controlled by gene transcription have mainly studied the regulation of transcription factors. However, there are examples in which the primary focus of biological regulation is at the level of a transcriptional coactivator. We have reviewed here the molecular mechanisms a...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2002-0012
更新日期：2003-02-01 00:00:00
abstract：:Access to effective affordable contraception is critical for individual and public health. A wide range of hormonal contraceptives (HCs), which differ in composition, concentration of the progestin component, frequency of dosage, and method of administration, is currently available globally. However, the options are r...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2017-00103
更新日期：2018-02-01 00:00:00
abstract：:Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Targeting the immune checkpoints cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) with inhibitory antibodies has demonstrated effective and durable antitumor ac...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2018-00006
更新日期：2019-02-01 00:00:00
abstract：:This paper has reviewed current knowledge of clinical, biochemical, and morphological manifestations of extracranial GRH-producing tumors. Excessive GRH release stimulates pituitary somatotrophs causing elevation of blood GH levels and acromegaly. In some patients with GRH-containing tumor, blood GH concentrations are...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/edrv-9-3-357
更新日期：1988-08-01 00:00:00
abstract：:We applied decision analysis to the controversy over the management of the solitary nonfunctioning thyroid nodule. Three standard management plans were considered: immediate subtotal thyroidectomy; a six month trial of thyroid suppression with L-thyroxine, with non-suppressible lesions being removed surgically; and as...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/edrv-5-2-185
更新日期：1984-04-01 00:00:00
abstract：:Cells from the chorionic girdle of the equine trophoblast invade the maternal endometrium at day 36 of gestation and become established as secretory elements known as the endometrial cups. These structures, which persist for 40-60 days, produce a gonadotropin which can be found in circulation until about day 130 of ge...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/edrv-12-1-27
更新日期：1991-02-01 00:00:00
abstract：:The most active corticosteroids are 11 beta-hydroxylated. Humans have two isozymes with 11 beta-hydroxylase activity that are respectively required for cortisol and aldosterone synthesis. CYP11B1 (11 beta-hydroxylase) is expressed at high levels and is regulated by ACTH, whereas CYP11B2 (aldosterone synthase) is norma...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/edrv-15-4-421
更新日期：1994-08-01 00:00:00
abstract：:Phosphate plays essential roles in many biological processes, and the serum phosphate level is tightly controlled. Chronic hypophosphatemia causes impaired mineralization of the bone matrix and results in rickets and osteomalacia. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate m...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2017-00220
更新日期：2018-06-01 00:00:00
abstract：:Hippo signaling is an evolutionarily conserved pathway that critically regulates development and homeostasis of various tissues in response to a wide range of extracellular and intracellular signals. As an emerging important player in many diseases, the Hippo pathway is also involved in the pathophysiology of diabetes...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2017-00167
更新日期：2018-02-01 00:00:00
abstract：:In recent years, much interest has been devoted to defining the role of the IGF system in the nervous system. The ubiquitous IGFs, their cell membrane receptors, and their carrier binding proteins, the IGFBPs, are expressed early in the development of the nervous system and are therefore considered to play a key role ...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2004-0024
更新日期：2005-12-01 00:00:00
